The role of the epigenetic mark H3K4me3 in human eggs and embryos
Epigenetic marks have been suggested to play an important role in embryo development. These marks regulate the transcription of genes, and decides which genes are switched on or off at what timepoint. Our research group recently showed that the epigenetic mark histone H3 lysine tri-methylation (H3K4me3) is essential for mouse embryo development. In this project, we wish to investigate whether the role of H3K4me3 in embryo development is conserved also in human. We use surplus material donated by patients, and perform chromatin immunoprecipitation followed by sequencing (ChIP-seq) optimized for low cell numbers to characterize the mark at different stages of human development. Our data suggest that H3K4me3 also plays an important role in human embryos, and that an abnormal H3K4me3 pattern may be linked to failed embryo development. A greater understanding of human egg and embryo development and the underlying regulatory mechanisms is of critical importance for basic reproductive biology and may guide future treatment strategies for IVF treatment.
New approaches in fertility preservation for cancer patients.
This project focuses on the use of low-input next-generation sequencing to investigate development of human immature eggs. One of the main aims is to determine how epigenetics are resolved in oocytes isolated from ovaries. It also includes developing new methods for activation of follicles and maturation of eggs prior ovarian tissue transplantation for cancer patients. Collectively, the goals of this research are to enhance our understanding of human eggs, which has been limited due to the avaibality of human samples. As well as improving the outcomes for the current fertility preservation protocols by increasing the number of high quality oocyte to develop into a healthy baby.
Fibroids and infertility
We we aim to explore some of the molecular factors that reduce fertility for women with leiomyomas, taking into account leiomyoma location, size, number and vascularity. Tissue samples from the endometrium and leiomyomas will be obtained during the mid-secretory phase before and 3-6 months after surgical excision for a comprehensive search for key molecular derangements.
Baseline medical information and standard questionnaire to record symptoms are collected from all participants and a gynaecological examination and a 2D and 3D vaginal ultrasonography including saline infusion sonography (SIS), if indicated, are performed. Blood samples for extraction of germ line DNA and for identification of possible biomarkers are taken.
Ovarian ageing and disease
Ovarian ageing is closely linked to the number of remaining follicles in the ovary and the genetic integrity of the oocytes enclosed in these follicles. Disorders and conditions that are related to increased or reduced number of ovarian follicles, like polycystic ovary syndrome (PCOS), ovarian endometriosis or unilateral oophorectomy, would be expected to slow or accelerate the rate of ovarian ageing. For example, polycystic ovaries are endowed with an increased number of follicles, and PCOS was suggested to prolong fertility of women treated with IVF. Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity, typically on the peritoneum or ovaries, and by inducing reactive inflammation it may interfere with follicle development. Removal of a single ovarian because of disease or for fertility preservation may also alter the dynamics of follicle depletion and ovarian ageing. We aim to study how PCOS, endometriosis, and removal of an ovary affect reproductive ageing and the outcome of infertility treatment.